The etiology of human large bowel cancer is unknown as are the specific mechanisms underlying this disease. The long term aims of this project are to develop insight into the key features of the carcinogenic process so that clues may be obtained whether the particular chemical carcinogens affecting the colon in experimental systems and factors modifying their metabolism might also be relevant to the human situation. In the present program, we propose to continue the identification of in vivo and in vitro metabolites of 1,2-dimethylhydrazine-14C and azoxymethane-14C so that the activation and detoxication pathways of these colon carcinogens can be exactly delineated. The influence of factors such as species, strain and sex, as well as of dietary influences (high and low fat, high and low protein, presence and absence of micronutrients such as selenium) and of germ-free status on these pathways will also be determined. The alkylation and subsequent alteration in important characteristics of selected macromolecules by these carcinogens will be studied. Since the last step in the metabolism of 1,2-dimethylhydrazine and of azoxymethane yields methylazoxymethanol, the fate of this compound in vivo and in vitro will also be studied.